Anti-inflammatory drugs and endothelial cell adhesion molecule expression in murine vascular beds

Background-Inflammatory bowel diseases (IBD) are characterised by an intens e infiltration of leucocytes that is mediated by adhesion molecules express ed on the surface of activated endothelial cells. Aims-To determine whether drugs used in the treatment of IBD, specifically dexamethasone (DEX), 5-aminosalicylic acid (5-ASA), methotrexate (MTX), and 6-mercaptopurine (6-MP), alter the expression of endothelial cell adhesion molecules (ECAMs). Methods-The expression of P-selectin, E-selectin, intercellular adhesion mo lecule 1 (ICAM-1), and vascular CAM 1 (VCAM-1) in different vascular beds o f C57B1/6J mice was measured using the dual radiolabelled monoclonal antibo dy technique. Results-Lipopolysaccharide (LPS) elicited a profound increase in the expres sion of all ECAMs in the mesentery, small intestine, caecum, and distal col on. The LPS induced increase in CAM expression was not significantly affect ed by prior treatment with either MTX or 6-MP. However, pretreatment with e ither DEX or 5-ASA significantly attenuated LPS induced increases in expres sion of P- and E-selectin, and VCAM-1 in the majority of tissues evaluated. DEX also blunted the LPS induced increase in ICAM-1 expression in the caec um and distal colon. DEX, but not 5-ASA, largely abolished the rise in plas ma tumour necrosis factor alpha elicited by LPS. Conclusions-These findings suggest that DEX and 5-ASA may exert their benef icial therapeutic action in IBD, at least in part, by inhibiting the expres sion of ECAMs which mediate leucocyte adhesion and transmigration in the mi crovasculature.